Wearable spectroscopy using filtered sensor

ABSTRACT

Methods and systems for spectroscopy are provided. Exemplary methods include: illuminating, with a tunable laser, an analyte with first light; detecting, with a filtered sensor, a first Raman signal; illuminating, with the tunable laser, the analyte using second light; detecting, with the filtered sensor, a second Raman signal, the second Raman signal being shifted from the first Raman signal by a second predetermined increment; illuminating, with the tunable laser, the analyte using third light; detecting, with the filtered sensor, a third Raman signal, the third Raman signal being shifted from the second Raman signal by the second predetermined increment; constructing a Raman spectrum using the first Raman signal, the second Raman signal, and the third Raman signal; and determining at least one molecule of the analyte using the Raman spectrum and a database of predetermined Raman spectra.

FIELD OF THE INVENTION

The present technology pertains to spectroscopy and more specifically tohigh-resolution spectroscopy using filtered image sensors.

BACKGROUND ART

The approaches described in this section could be pursued but are notnecessarily approaches that have previously been conceived or pursued.Therefore, unless otherwise indicated, it should not be assumed that anyof the approaches described in this section qualify as prior art merelyby virtue of their inclusion in this section.

Spectroscopy (or spectrography) refers to techniques that employradiation in order to obtain data on the structure and properties ofmatter. Spectroscopy involves measuring and interpreting spectra thatarise from the interaction of electromagnetic radiation (e.g., a form ofenergy propagated in the form of electromagnetic waves) with matter.Spectroscopy is concerned with the absorption, emission, or scatteringof electromagnetic radiation by atoms or molecules.

Spectroscopy can include shining a beam of electromagnetic radiationonto a desired sample in order to observe how it responds to suchstimulus. The response can be recorded as a function of radiationwavelength, and a plot of such responses can represent a spectrum. Theenergy of light (e.g., from low-energy radio waves to high-energygamma-rays) can result in producing a spectrum.

SUMMARY OF THE INVENTION

This summary is provided to introduce a selection of concepts in asimplified form that are further described in the Detailed Descriptionbelow. This summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used as an aid in determining the scope of the claimed subjectmatter.

The present disclosure is related to various systems and methods forspectroscopy. Specifically, a method for spectroscopy may comprise:illuminating, with a tunable laser, an analyte with first light, thefirst light having a first excitation wavelength; detecting, with afiltered sensor, a first Raman signal; illuminating, with the tunablelaser, the analyte using second light, the second light having a secondexcitation wavelength, the second excitation wavelength being largerthan the first excitation wavelength by a first predetermined increment;detecting, with the filtered sensor, a second Raman signal, the secondRaman signal being shifted from the first Raman signal by a secondpredetermined increment; illuminating, with the tunable laser, theanalyte using third light, the third light having a third excitationwavelength, the third excitation wavelength being larger than the secondexcitation wavelength by the first predetermined increment; anddetecting, with the filtered sensor, a third Raman signal, the thirdRaman signal being shifted from the second Raman signal by the secondpredetermined increment. The method for spectroscopy may furthercomprise: constructing a Raman spectrum, with a computing system, usingthe first Raman signal, the second Raman signal, and the third Ramansignal; and determining at least one molecule of the analyte, with thecomputing system, using the Raman spectrum and a database ofpredetermined Raman spectra.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments are illustrated by way of example, and not by limitation, inthe figures of the accompanying drawings, in which like referencesindicate similar elements and in which:

FIGS. 1A-C are simplified block diagrams of spectrometers, according tosome embodiments.

FIG. 2 is a simplified block diagram of a wearable spectroscopy system,according to various embodiments.

FIGS. 3A-C are simplified representations of filtered image sensors, inaccordance with some embodiments.

FIG. 4 is an alternate view of the system of FIG. 2, in accordance withvarious embodiments.

FIGS. 5A and 5B are graphical representations of penetration depth intoliquid water and absorption spectra of biological tissues, respectively,according to some embodiments.

FIGS. 6A and 6B depict a Raman spectrum and a shifted Raman spectrum,respectively, according to various embodiments.

FIGS. 7A and 7B show an example program for determining a number offilters, a number of steps, and a step size, in accordance with someembodiments.

FIG. 8 is a graph of a simulated and an actual Raman spectrograph.

FIG. 9 illustrates a flow diagram of a method for spectroscopy using afiltered sensor, according to some embodiments.

FIG. 10 is a simplified block diagram of a computing system, accordingto various embodiments.

DETAILED DESCRIPTION

While this technology is susceptible of embodiment in many differentforms, there is shown in the drawings and will herein be described indetail several specific embodiments with the understanding that thepresent disclosure is to be considered as an exemplification of theprinciples of the technology and is not intended to limit the technologyto the embodiments illustrated. The terminology used herein is for thepurpose of describing particular embodiments only and is not intended tobe limiting of the technology. As used herein, the singular forms “a,”“an,” and “the” are intended to include the plural forms as well, unlessthe context clearly indicates otherwise. It will be further understoodthat the terms “comprises,” “comprising,” “includes,” and/or“including,” when used in this specification, specify the presence ofstated features, integers, steps, operations, elements, and/orcomponents, but do not preclude the presence or addition of one or moreother features, integers, steps, operations, elements, components,and/or groups thereof. Like or analogous elements and/or components,referred to herein, may be identified throughout the drawings with likereference characters. In addition, several of the figures are merelyschematic representations of the present technology. As such, some ofthe components may have been distorted from their actual scale forpictorial clarity.

FIGS. 1A-1C depict various spectrometers 100A-100C, according to someembodiments. For example, spectrometers 100A and 100C are opticalsystems having two lenses/mirrors 130A+150A and 130C+150C (respectively)that produce an image of input slit 110A and 110C (respectively) ondetector 160A and 160C (respectively). In between lenses/mirrors130A+150A and 130C+150C is diffraction grating 140A and 140C(respectively) which disperses different wavelengths at differentangles. The dispersion causes different wavelengths of light 120A and120C entering input slit 110A and 110C (respectively) to be imaged ondifferent positions on detector 160A and 160C (respectively). Detectors160A and 160C can use light focused onto them to measure the intensityof particular spectrum of light 120A and 120C (respectively). Inspectrometer 100B, grating 140B can be concave and act as both adispersive and focusing element. Grating 140B focuses and disperseslight 120B entering input slit 110E to be imaged on different positionson detector 160B.

To operate, spectrometers 100A-100C employ a three-dimensionalarrangement of bulk optics (e.g., lenses, mirrors, gratings, etc.). Thebulk optics can be large and heavy. For example, Raman spectroscopytypically requires high resolution, on the order of 5-10 wave numbers.As spectrometers 100A-100C become smaller, resolution is lost, such asfrom reduced focal lengths of some bulk optics. Were spectrometers100A-100C reduced to a 5 cm×5 cm area, the resolution would be on theorder of 20-40 wave numbers. Accordingly, for some applicationsspectrometers 100A-100C have the disadvantage of large size (e.g., theycannot be worn like a watch, fitness tracker, smart watch, and thelike).

FIG. 2 is a simplified block diagram of wearable spectroscopy system200, according to some embodiments. System 200 includes spectrometer210, analyte 240, and optional computing system 295. Spectrometer 210can include opening 212, optional band 214, case (or housing) 216,excitation light source 220, beam splitter 260, filter 270, detector280, and electronics 290. Spectroscopy system 200 is described below inrelation to Raman spectroscopy purely for illustrative purposes and notlimitation. Embodiments of spectroscopy system 200 can be used for otherspectroscopy applications.

According to some embodiments, excitation light source 220 is amonochromatic light source, such as a laser. For example, excitationlight source 220 is at least one of an Nd:YAG (neodymium-doped yttriumaluminium garnet; Nd:Y3Al5O12), Argon-ion, He—Ne, and diode laser. Byway of further non-limiting example, excitation light source 220 canprovide light (electromagnetic waves) in a range between ultra-violet(UV) light (e.g., electromagnetic radiation with a wavelength from 10 nmto 400 nm) and shortwave near-infrared (NIR) (1.4 μm to 3 μm), includingportions of the electromagnetic spectrum in-between, such as visiblelight (e.g., 380 nm-760 nm) and NIR light (e.g., 0.75 μm to 1.4 μm).

Excitation light source 220 can be tunable—a wavelength of the lightfrom excitation light source 220 is changed by one or more(predetermined) increments and/or to one or more (predetermined)values—such as by using temperature (heat) control (e.g., from a heatingelement), electrical control (e.g., using microelectromechanical systems(MEMS)), and mechanical control (e.g., using a mechanism to turn amirror). In various embodiments, excitation light source 220 is in atransistor outline (TO) package have three leads: anode, cathode, andground. Preferably, excitation light source 220 provides high spectralpurity, high wavelength stability, and/or high power stability output.

Using Raman spectroscopy as a non-limiting example, Raman signalstrength is proportional to the power of the Raman laser (in milliwattsor mW) exciting the sample. In other words, the more laser power used,the larger the Raman signal will advantageously be. According to variousembodiments, the power of excitation light source 220 can be in a rangeof 120 mW-1,000 mW.

Opening 212 can include an aperture in case 216. In some embodiments,the aperture can be in the form of a pinhole (e.g., circle), rectangle(e.g., (sharp-edged) slit), and other shapes. For example, the pinholecan be 10 μm-5,000 μm in diameter. By way of further non-limitingexample, the rectangle can have a width in a range of 10 μm-5,000 μm anda length in a range of 500 μm-15,000 μm. The shape and size of theaperture can be compatible (e.g., match or mate) with filter 270 and theoptical magnification of spectrometer 210.

In some embodiments, the aperture is an air aperture, air pinhole, airslit, and the like (e.g., open to the air, uncovered). Alternatively,opening 212 can include a window to prevent contaminants (e.g.,moisture, dust, dirt, and the like) from entering case 216, such as forwater and/or dust resistance. In various embodiments, the window can beplexiglass, mineral glass, quartz, synthetic sapphire, and the like. Thewindow can transmit (e.g., does not block or filter) light 230 and light250.

Beam splitter 260 can be an optical device which reflects some light andpasses other light (e.g., based upon the light's angle of incidence).For example, beam splitter 260 can reflect light 230 from excitationlight source 220 through opening 212 and onto analyte 240. By way offurther non-limiting example, beam splitter can transmit light 250(e.g., Raman scatter) to detector 280 through filter 270. Beam splitter260 can be made of glass or plastic, and include a transparently thincoating of dielectric material(s) and/or metal (e.g., aluminum,magnesium, and the like).

Filter 270 transmits a particular wavelength (or range of wavelengths)of light to detector 280 (and blocks the rest). As illustrated in FIGS.3A-3C, filter 270 can be a one-dimensional, two-dimensional, orthree-dimensional array of separate filters, each filter transmittinglight centered around a different (or same) wavelength (A) to detector280. Filter 270 can be disposed on detector 280. For example, (theconstituent filters of) filter 270 can be a thin-film coating—on theorder of nanometers to microns thick—deposited onto filter 270 usingthin-film deposition techniques. By way of further non-limiting example,(the constituent filters of) filter 270 can be made of glass or plastic,cut, and mounted onto detector 280. (The constituent filters of) Filter270 can be any transparent material that transmits electromagneticradiation centered around a particular wavelength or a (narrow) range ofwavelengths (and blocks the rest).

Detector 280 receives light 250 and measures the intensity of scatteredlight. Detector 280 can be a one-, two-, or three-dimensional detectorarray comprised of a semiconductor material such as silicon (Si) andindium gallium arsenide (InGaAs). In some embodiments, a bandgap energyof the semiconductor determines an upper wavelength limit of detector280. An array of detector 280 can be in different configurations, suchas charged coupled devices (CCDs), back-thinned charge coupled devices(BT-CCDs), complementary metal-oxide-semiconductor (CMOS) devices, andphotodiode arrays (PDAs). CCDs can be one or more of intensified CCDs(ICCDs) with photocathodes, back illuminated CCDs, and CCDs with lightenhancing coatings (e.g., Lumogen® from BASF®). Detector 280 can have aresolution of 8-15 wavenumbers, according to some embodiments. Detector280 can be used to detect concentrations of molecules in a range of 1mg-1,000 mg per deciliter (mg/dL).

By way of further non-limiting example, detector 280 is a single pixeltime-gated detector such as single-photon avalanche diode (SPAD),micro-channel plate (MCP), photomultiplier tube (PMT), siliconphotomultiplier (SiPM), or avalanche photodiode (APD) that sits on ascanning motor driven rail, or detector arrays such as a single-photonavalanche diode (SPAD) array, or an intensified CCD (ICCD). A SPAD is asolid-state photodetector in which a photon-generated carrier (via theinternal photoelectric effect) can trigger a short-duration butrelatively large avalanche current. The leading edge of the avalanchepulse marks the arrival (time) of the detected photon. The avalanchecurrent can continue until the avalanche is quenched (e.g., by loweringa bias voltage down to a breakdown voltage). According to variousembodiments, each pixel in some SPAD arrays can count a single photonand the SPAD array can provide a digital output (e.g., a 1 or 0 todenote the presence or absence of a photon for each pixel).

To detect another photon, electronics 290 can be used to read outmeasurements and quench the SPAD. For example, electronics 290 can sensethe leading edge of the avalanche current, generate a (standard) outputpulse synchronous with the avalanche build up, quench the avalanche, andrestore the diode to an operative level. Electronics 290 can providepassive quenching (e.g., passive quenching passive reset (PQPR), passivequench active reset (PQAR), and the like) and/or active quenching (e.g.,active quench active reset (AQAR), active quenching passive reset(AQPR), and the like). In various embodiments, detector 280 is acomplementary metal-oxide semiconductor (CMOS) SPAD array.

A micro-channel plate (MCP) is a planar component used for detection ofsingle particles, such as photons. An MCP can intensify photons by themultiplication of electrons via secondary emission. Since a microchannelplate detector has many separate channels, it can also provide spatialresolution.

A photomultiplier tube (PMT) is a photoemissive device which can detectweak light signals. In a PMT, absorption of a photon results in theemission of an electron, where the electrons generated by a photocathodeexposed to a photon flux are amplified. A PMT can acquire light througha glass or quartz window that covers a photosensitive surface, called aphotocathode, which then releases electrons that are multiplied byelectrodes known as metal channel dynodes. At the end of the dynodechain is an anode or collection electrode. Over a very large range, thecurrent flowing from the anode to ground is directly proportional to thephotoelectron flux generated by the photocathode.

Silicon photomultipliers (SiPM) are solid-state single-photon-sensitivedevices based on Single-photon avalanche diode (SPAD) implemented on acommon silicon substrate. Each SPAD in an SiPM can be coupled with theothers by a metal or polysilicon quenching resistor.

Avalanche photodiodes (APDs) are semiconductor photodiodes with aninternal gain mechanism. In an APD, absorption of incident photonscreates electron-hole pairs. A high reverse bias voltage creates astrong internal electric field, which accelerates the electrons throughthe semiconductor crystal lattice and produces secondary electrons byimpact ionization. The resulting electron avalanche can produce gainfactors up to several hundred.

An intensified charge-coupled device (ICCD) is a CCD that is opticallyconnected to an image intensifier that is mounted in front of the CCD.An image intensifier can include three functional elements: aphotocathode, a micro-channel plate (MCP) and a phosphor screen. Thesethree elements can be mounted one close behind the other. The photonswhich are coming from the light source fall onto the photocathode,thereby generating photoelectrons. The photoelectrons are acceleratedtowards the MCP by an electrical control voltage, applied betweenphotocathode and MCP. The electrons are multiplied inside of the MCP andthereafter accelerated towards the phosphor screen. The phosphor screenconverts the multiplied electrons back to photons which are guided tothe CCD by a fiber optic or a lens. An image intensifier inherentlyincludes shutter functionality. For example, when the control voltagebetween the photocathode and the MCP is reversed, the emittedphotoelectrons are not accelerated towards the MCP but return to thephotocathode. In this way, no electrons are multiplied and emitted bythe MCP, no electrons are going to the phosphor screen, and no light isemitted from the image intensifier. In this case no light falls onto theCCD, which means that the shutter is closed.

Detector 280 can be other photodetectors having a time resolution ofabout one nanosecond or less. By way of further non-limiting example,detector 280 is a streak camera array, which can have a time-resolutionof around 180 femtoseconds. A streak camera measures the variation in apulse of light's intensity with time. A streak camera can transform thetime variations of a light pulse into a spatial profile on a detector,by causing a time-varying deflection of the light across the width ofthe detector.

A spectral resolution of a spectrum measured by detector 280 can dependon the number of pixels (e.g., discrete photodetectors) in detector 280.A greater number of pixels can provide a higher spectral and spatialresolutions. Detector 280 can comprise a one-dimensional, two-, orthree-dimensional array of pixels. For example, detector 280 can be in arange of 32 to 1,048,576 pixels, or even 2,099,152 pixels.

Electronics 290 can include a power source (e.g., (rechargeable)lithium-ion battery) and computing system (not depicted in FIG. 2). Invarious embodiments, electronics 290 includes a system on a chip (SoC)(not depicted in FIG. 2). An SoC is an integrated circuit that includes(all) components of a computer system on a single substrate. Thecomponents can include assorted combinations of a central processingunit (CPU), memory, input/output ports, secondary storage, and digital,analog, mixed-signal, and radio frequency signal processing functions.For example, electronics 290 can optionally include circuits for wiredand/or wireless communications (e.g., with computing system 295).Electronics can optionally include circuits and interfaces for wiredand/or wireless (inductive) charging of the power source.

Electronics 290 can optionally include a control surface (e.g., physicalor virtual push button/switch) and/or a display (e.g., touch display)for receiving inputs and/or providing outputs to a user. Computingsystems are described further in relation to FIG. 8. Electronics 290 canbe coupled to excitation light source 220 and detector 280, such as forpower, data, and control purposes. In various embodiments, when ameasurement is to be taken (e.g., input is received from a user,periodic measurement controlled by electronics 290, etc.), electronics290 can control excitation light source 220 to provide light 230 (e.g.,emit a laser pulse). A predetermined amount of time after light 230 isprovided, electronics 290 can provide a signal directing detector 280 to(effectively) stop detecting and provide measurements (e.g., report aphoton count at that time). For example, the predetermined amount oftime can be selected using the duration of light 230 (e.g., a laserpulse), characteristics of analyte 240 (e.g., duration/lifetime offluorescence), and the like.

Shapes and a spatial arrangement of the constituent parts ofspectrometer 210 (e.g., excitation light source 220, beam splitter 260,filter 270, detector 280 (sometimes referred to herein as sensor 280),and electronics 290) are shown in FIG. 2 purely for illustrativepurposes and not limitation. Other shapes and arrangements can be used.Having filter 270 disposed on sensor 280, advantageously allows a one-or two-dimensional arrangement of opening 212, beam splitter 260, filter270, and sensor 280. Moreover, bulk optics (and their associated sizeand weight) are not required by spectrometer 210. According to variousembodiments, case (or housing) 216 of spectrometer 210 can beapproximately 30 mm-50 mm wide (width) and 5 mm-20 mm thick (thickness).Case 216 can be made of metal (e.g., platinum, gold, gold plate, silver,stainless steel, titanium, tungsten carbide, etc.), ceramic, tantalum,plastic, and combinations thereof.

Spectrometer 210 can provide information about molecular vibrations toidentify and quantify characteristics (e.g., molecules) of analyte 240.Spectrometer 210 can direct light (electromagnetic waves) 230 fromexcitation light source 220 onto analyte 240. Light 230 from excitationlight source 220 can be said to be shone on analyte 240 and/or analyte240 can be said to be illuminated by excitation light source 220 and/orlight 230. When (incident) light from excitation light source 220 hitsanalyte 240, the (incident) light scatters. A majority (e.g.,99.999999%) of the scattered light is the same frequency as the lightfrom excitation light source 220 (e.g., Rayleigh or elastic scattering).

A small amount of the scattered light (e.g., on the order of 10⁻⁶ to10⁻⁸ of the intensity of the (incident) light from excitation lightsource 220) is shifted in energy from the frequency of light 230 fromexcitation light source 220. The shift is due to interactions between(incident) light 230 from excitation light source 220 and thevibrational energy levels of molecules in analyte 240. (Incident) Light230 interacts with molecular vibrations, phonons, or other excitationsin analyte 240, causing the energy of the photons (of light 230 fromexcitation light source 220) to shift up or down (e.g., Raman orinelastic scattering). Light 250 can include, for example, at least oneof Raman scatter, fluorescence, and Rayleigh scattering. The shift inenergy of light 250 (e.g., Raman scatter from analyte 240) can be usedto identify and quantify characteristics (e.g., molecules) of analyte240.

System 200 can include computing system 295. According to variousembodiments, computing system 295 can be communicatively coupled tospectrometer 210 using various combinations and permutations of wiredand wireless communications (e.g., networks) described below in relationto FIG. 8. In some embodiments, computing system 295 can include adatabase of Raman spectra associated with known molecules and/orremotely access the database over a communications network (not shown inFIG. 2). Computing system 295 can receive intensity measurements fromspectrometer 210, produces at least one Raman spectrum using data (e.g.,intensity measurements) from spectrometer 210, and identifies and/orquantifies molecules in analyte 240 using the at least one Ramanspectrum and a database of Raman spectra associated with knownmolecules.

In some embodiments, computing system 295 is a single computing device.For example, computing system 295 is a desktop or notebook computercommunicatively coupled to Spectrometer 210 through a Universal SerialBus (USB) connection, a Wi-Fi connection, Bluetooth and the like. Invarious embodiments, computing system 295 can be various combinationsand permutations of stand-alone computers (e.g., smart phone, phablet,tablet computer, notebook computer, desktop computer, etc.) andresources in a cloud-based computing environment. For example, computingsystem 295 is a smart phone and a cloud-based computing system. Thesmart phone can receive data (e.g., intensity measurements) fromspectrometer 210 using USB, Wi-Fi, Bluetooth, and the like. The smartphone can optionally produce at least one Raman spectrum using the data.The smart phone can transmit the data and/or at least one Raman spectrumto a cloud-based computing system over the Internet using a wirelessnetwork (e.g., cellular network). The cloud-based computing system canproduce at least one Raman spectrum using the data and/or quantifyand/or identify molecules in analyte 240 using the recovered Ramanspectrograph.

Computing system 295 can alternatively or additionally be a cloudcomputing system which receives data (e.g., intensity measurements) fromspectrometer 210 (using USB, WiFi, Bluetooth, cellular network and thelike), produce at least one Raman spectrograph using the data, andquantify and/or identify molecules in analyte 240 using the Ramanspectrograph. Computing system 295 is described further in relation toFIG. 8.

According to some embodiments, analyte 240 is at least one of solid,liquid, plant tissue, human tissue, and animal tissue. For example,animal tissue is one or more of epithelial, nerve, connective, muscle,and vascular tissues. By way of further non-limiting example, planttissue is one or more of meristematic (e.g., apical meristem andcambium), protective (e.g., epidermis and cork), fundamental (e.g.,parenchyma, collenchyma and sclerenchyma), and vascular (e.g., xylem andphloem) tissues. Purely for the purposes of illustration and notlimitation, analyte 240 is depicted as a cross-section of a human limb,such as a wrist, and includes blood vessel 242 and blood 244. Band 214can be used secure spectrometer 210 to analyte 240 (e.g., the wrist).For example, spectrometer 210 is in contact with analyte 240 (e.g.,spectrometer 210 is no more than 1 cm from analyte 240). Band 214 can bemade from metal, plastic, and combinations thereof.

FIGS. 3A-3C illustrate configurations of filter 270 and detector 280(FIG. 2) according to some embodiments. FIG. 3A shows configuration 300Awith filter 270A disposed on sensor 280A (e.g., a 1×1 arrangement).Filter 270A transmits light (in a wavelength range) centered aroundwavelength A. FIG. 3B depicts configuration 300B with filters270B₁-270B_(n) disposed on sensor 280B (e.g., a 1×n array). Filters270B₁-270B_(n) transmit light (in a wavelength range) centered aroundwavelengths λ₁-λ_(n), respectively. FIG. 3C shows configuration 300Cwith filters 270C_(1,1)-270C_(x,y) disposed on sensor 280C (e.g., an x×yarray). Filters 270C_(1,1)-270C_(x,y) transmit light (in a wavelengthrange) centered around wavelengths λ_(1,1)-λ_(x,y), respectively.Although filters 270A, 270B₁-270B_(n), and 270C_(1,1)-270C_(x,y) areshown in FIGS. 3A, 3B, and 3C (respectively) as having a roughly squareshape, other shapes such as circles, rectangles, and other polygons canbe used.

FIG. 4 shows system 400, which is a simplified alternate view of system200 (FIG. 2), in accordance with some embodiments. System 400 includesspectrometer 210A and analyte 240A. Spectrometer 210A has at least someof the characteristics of spectrometer 210 (FIG. 2). Analyte 240A has atleast some of the characteristics of analyte 240 (FIG. 2).

Analyte 240A can include layers, such as epidermis 410, dermis 430, andsubcutaneous (fatty) tissue 440. Dermis 430 includes blood vessel 420(e.g., vein and/or artery). For pictorial clarity, some features ofepidermis 410, dermis 430, and subcutaneous (fatty) tissue 440 (e.g.,hair shaft, sweat pore and duct, sensory nerve ending, sebaceous gland,pressure sensor, hair follicle, stratum, and the like) are not shown inFIG. 4.

Light 230A can have at least some of the characteristics of light 230(FIG. 2). Light 250A can have at least some of the characteristics oflight 250 (FIG. 2). Light 230A (e.g., from excitation light source 220(FIG. 2)) illuminates analyte 240A. Light 230A can pass throughepidermis 410 to dermis 430. Photons of light can bounce off moleculesinside blood vessel 420. (Resulting) Light 250A (e.g., Raman scatteramong others) is received by detector 280 (FIG. 2).

An optimal location for taking blood measurements is where the blood is,for example, blood vessel 420. Measurement accuracy can be compromisedwhen light 230A overshoots or undershoots blood vessel 420. In humanbeings, blood vessel 420 is on the order of 80 μm thick and epidermis410 is on the order of 200 μm, so it is easy to overshoot and/orundershoot blood vessel 420 (e.g., misses blood vessel 420). Sincespectrometer 210A is worn on a limb (e.g., using band 214 (FIG. 2), thedistance from spectrometer 210A to blood vessel 420 does not appreciablychange, ensuring light 230A bounces off of blood vessel 420 and aquality measurement can be taken.

Details of analyte 240A, such as epidermis 410, dermis 430, andsubcutaneous (fatty) tissue 440, are provided purely by way of exampleand not limitation. Analyte 240A can include other, more, and/or fewerdetails than those illustrated in FIG. 4. Moreover, analyte 240A isdepicted as human tissue purely for illustrative purposes and notlimitation.

FIG. 5A is a graphical representation (e.g., plot, graph, and the like)500A of penetration depth 510A into liquid water of light overexcitation wavelength. By way of non-limiting example, an epidermis(e.g., epidermis 410 in FIG. 4) can have a thickness on the order of 100μm, so an excitation wavelength of light (e.g., light 230 and light 230Ain FIGS. 2 and 4, respectively) can be advantageously selected such thata penetration depth is at least 100 μm (e.g., approximately 190 nm to2400 nm). In some embodiments, the excitation wavelength of light is ina range of 670 nm-900 nm for (human) tissue. Other ranges for theexcitation wavelength of light can be used (e.g., depending on the depthof the tissue to be studied).

FIG. 5B is a graphical representation (e.g., plot, graph, and the like)500B of absorption spectra of various tissues over excitationwavelength. By way of non-limiting example, an excitation wavelength oflight (e.g., light 230 and light 230A in FIGS. 2 and 4, respectively)can be advantageously selected to minimize the absorption coefficient soas to minimize absorption of the light by the tissue to be studied(e.g., so the light can scatter and be detected). When the tissuesubstantially absorbs light and/or Raman scatter (among others) (e.g.,250 and 250A in FIGS. 2 and 4, respectively), there can be insufficientRaman electromagnetic radiation for detector 280 (FIG. 2) to detect. Forexample, in skin tissue that has highly fluorescent chromophores, theincreased absorption amplifies the emitted fluorescence and masks theweaker Raman signal. In various embodiments, the excitation wavelengthof light is in a range of 670 nm-900 nm for (human) tissue. Other rangesfor the excitation wavelength of light can be used (e.g., depending onthe absorption coefficient of the tissue to be studied).

In embodiments where analyte (e.g., 240 and 240A (FIGS. 2 and 4)) isalive (and not dead) animal (e.g., living, alive, etc.), blood 244 flowsthrough blood vessel 242 and 420 (FIGS. 2 and 4). Blood flow throughblood vessel 242 and 420 in animals (e.g., humans) is caused by a heart(not shown in FIG. 4) pumping blood (e.g., beating heart). Whenmeasurements are taken at a rate slower than blood flows, differentsamples of blood are measured instead of the same sample.

When spectrometer 210 and 210A (FIGS. 2 and 4) takes multiplemeasurements, the measurements can be taken before the molecules inblood illuminated in one measurement (e.g., blood sample) flow away andare not available for the next measurement. For example, a resting adulthuman heart can beat at approximately 60 to 100 beats a minute (˜1 Hz).Spectrometer 210 and 210A can take measurements within a tenth of asecond (˜0.1 KHz) or less, such that measurements are taken faster thanblood flows (e.g., multiple measurements are taken from the same(instead of different) sample). Slower and/or faster sampling rates(e.g., frequency at which measurements are taken) can be used dependingon the heart rate associated with analyte 240 and 240A (FIGS. 2 and 4).In various embodiments, the sampling rate is 10 Hz-1 KHz.

FIGS. 6A and 6B are graphical representations (e.g., plot, graph, andthe like) 600A and 600B of received light intensity (in milliwatts (mW),other units can be a.u. (arbitrary units of intensity) and photon count)(along axis 620) over received light (Raman shift) wavelength (innanometers (nm), other units can be wavenumber in cm⁻¹) (along axis610), according to some embodiments. Graph 600A includes Raman signal630A₁-630A₁₂, collectively referred to as Raman signal 630A. Graph 600Bincludes Raman signal 630B₁-630B₁₂, collectively referred to as Ramansignal 630B. Raman signals 630A and 630B are Raman spectrographs foranalyte 240 and 240A (FIGS. 2 and 4). Purely for illustration, Ramansignals 630A and 630B are shown having peaks at regular intervals, butRaman signals 630A and 630B may have any number of peaks havingdifferent intensities and occurring at different/irregular frequencies.Raman signals 630A and 630B can result from excitation light source 220emitting light (e.g., laser light) at different excitation wavelengths(A).

(Each constituent filter of) Filter 270 (FIG. 2) cannot be too narrow(e.g., in terms of full width at half maximum (FWHM)), because there maybe insufficient resolution for some applications. Windows 640 ₁-640 ₄represent portions of Raman signals 630A and 630B which pass through(constituent filters of) filter 270. Window 640 ₁ is centered aboutwavelength λ₁, window 640 ₂ about wavelength λ₂, window 640 ₃ aboutwavelength λ₃, and window 640 ₄ about wavelength λ₄. Although fourwindows 640 ₁-640 ₄ are shown in FIGS. 6A and 6B, any number of windows(corresponding to the number of constituent filters of filter 270) canbe used. As shown in FIGS. 6A and 6B, windows 640 ₁-640 ₄ may not coverall of Raman signals 630A and 630B (e.g., the resolution is low).

To compensate for the low resolution, the excitation wavelength ofexcitation light source 220 (FIG. 2) can be tuned. When the excitationwavelength is shifted by step Δλ (which can be referred to as a walkingstep), the spectrum (Raman signals 630A and 630B) will follow the lasershift. The whole Raman spectrum shifts by the same amount as the laserwavelength shift/step. In addition, the Raman spectrum remains the same(just shifted), regardless of the excitation wavelength. That is, thesame molecules in analyte 240 are measured with each laser pulse (e.g.,light 230 in FIG. 2), so the Raman spectrum is the same (just shifted)with each laser pulse.

FIG. 6A shows an initial measurement (Raman spectrum) and FIG. 6B showsa subsequent measurement (Raman spectrum)—shifted by step Δλ—taken afterexcitation light source 220 is shifted by step Δλ. With each step Δλ,windows 640 ₁-640 ₄ cover a portion of the spectrum not covered by thepreceding step(s). By shifting the excitation wavelength of excitationlight source 220, the spectrum (e.g., Raman signals 630A and 630B) isshifted. By shifting (multiple times), the spectrum can be fully coveredby windows 640 ₁-640 ₄. Since step Δλ is predetermined to cover thespectrum (Raman signals 630A and 630B), the spectrum can be constructed(stitched together) from the measurements (e.g., fraction of thespectrum) taken each time excitation light source 220 is shifted by stepΔλ.

The size of Δλ (e.g., how far (range of) excitation light source 220(FIG. 2) is tuned), number of constituent filters in filter 270 (FIG. 2)and hence the number of windows, and the width (e.g., in terms of FWHM)of the filters can be traded off amongst each other. An excitation lightsource tunable over a large range requires a larger laser. A largerarray size (number of constituent filters) for filter 270 reduces thenumber of steps that are taken. Narrower constituent filters of filter270 can reduce the size of step Δλ and the filter array size. Purely forthe purpose of illustration and not limitation, Table 1 shows the numberof filters, the number of steps, and the step size (Δλ), where theconstituent filters (e.g., of filter 270 in FIG. 2) have a FWHMbandwidth in a range from approximately 0.1 nm to 0.7 nm:

TABLE 1 NUMBER OF FILTERS NUMBER OF STEPS STEP SIZE (Δλ) (nm) 4 24 0.1 824 0.2 16 20 0.4 32 20 0.4 64 16 0.4 128 8 0.4 256 4 0.5 512 2 0.6 10242 0.6 2048 1 0.7

FIGS. 7A and 7B illustrate code 700A and 700B for calculating a numberof filters, a number of steps, and a step size, such as are shown abovein Table 1. For example, to cover a range of Raman shift from 300 cm⁻¹to 1800 cm⁻¹ wavenumber, using a 980 nm excitation pulse and a filterhaving a FWHM bandwidth of 2 nm, the number of filters can be determinedwith the number of the laser wavelength steps tuned (wavelengthinterval), which can be similar to the filter bandwidth. If 4 steps (oftuned laser wavelengths) are used, then the wavelength separation of thefilter can be every 2×4=8 nm. Code 700A and 700B can be used to study,for example, the tradeoff between a number of filters and a number ofsteps, and determine suitable combinations for different applications.

In some embodiments, the spectrometer resolution (e.g., spectrometer 210in FIG. 2) is equal to or slightly worse than the filter (e.g., filter270) bandwidth. FIG. 8 illustrates a graphical representation (e.g.,plot, graph, and the like) 800 of simulated Raman spectrum 810 andactual Raman spectrum 820 for Benzonitrile (C₇H₅N or C₆H₅(CN)). In theexample of FIG. 8, simulated Benzonitrile spectra 810—from a 980 nmexcitation pulse, filter size of 2 nm, and four tuned laser steps of 980nm, 982 nm, 984 nm, and 986 nm—is shown with actual Benzonitrile spectra820. The spectral resolution of simulated Benzonitrile spectra 810 isaround 19 cm⁻¹, which is slightly worse, but very close to 2 nm. Thetotal wavelength range in nm for 300 cm⁻¹ 1800 cm⁻¹ can be ˜181 nm, thusthe total number of narrowband filters should be 181÷8=22.5, thus atleast 23 filters can be used.

FIG. 9 illustrates a method 900 for spectroscopy using a filteredsensor, according to some embodiments. Method 900 can be performed byspectrometer 210 and 210A (FIGS. 2 and 4) and/or computing system 295(FIG. 2). Method 900 can commence at step 910, where an analyte can beilluminated using light having an initial excitation wavelength. Forexample, the analyte has at least some of the characteristics analyte240 and 240A (FIGS. 2 and 4). By way of further non-limiting example,the light can be provided by spectrometer 210 and/or 210A, for example,using excitation light source 220 (FIG. 2). For illustrative purposes,the initial excitation wavelength can referred to as λ₀ and can have avalue of 670 nm (e.g., λ₀=670 nm). Other values for λ₀ can be used.

At step 920, a spectrum (e.g., including Raman scattering (or Ramansignal)) can be detected from the illuminated analyte. In someembodiments, the light hitting the analyte results in Raman scattering(or Raman signal). For example, the Raman scattering (e.g., light 250and 250A in FIGS. 2 and 4, respectively) can be detected by spectrometer210 and 210A (e.g., using detector 280 through filter 270 (FIG. 2)). Byway of further non-limiting example, the detected Raman scattering mayappear (e.g., when graphed, plotted, and the like) in/through windows640 ₁-640 ₄, as shown in graph 600A (FIG. 6A) (where the excitationwavelength is Δ₀). The detected spectrum (e.g., data, graphicalrepresentation, and the like) can be stored by and/or in spectrometer210 and 210A, and/or computing system 295.

At step 930, the preceding excitation wavelength can be increased ordecreased by a predetermined increment or decrement, respectively. Forillustrative purposes, the predetermined increment/decrement can bereferred to as Δλ. For example, when the preceding excitation wavelengthis λ₀, an increased/decreased excitation wavelength is λ₁, whereλ₁=λ₀±Δλ. The detected Raman scattering may appear (e.g., when graphed,plotted, and the like) in/through windows 640 ₁-640 ₄, as shown in graph600B (FIG. 6B) (where the excitation wavelength is λ₁). By way offurther non-limiting example, when the preceding excitation wavelengthis λ₁, an increased/decreased excitation wavelength is λ₂, whereλ₂=λ₁±Δλ. By way of additional non-limiting example, when N spectra areto be detected, λ_(A)=λ₀±(A*Δλ), where A={0, 1, . . . (N−1)}.

By way of illustration and not limitation, the predeterminedincrement/decrement can have a value of 0.5 nm. To illustrateembodiments where the excitation wavelength is increased, when λ₀=670nm, λ₁=670.5 nm, λ₂=671 nm, and so on according to the number of spectrato be detected (N). In some embodiments, the excitation wavelength isdecreased by a decrement.

At step 940, the analyte can be illuminated using light having theincreased or decreased wavelength. To illustrate embodiments where theexcitation wavelength is increased, the light can have a wavelengthλ1=670.5 nm, λ2=671 nm, or so on according to the number of spectra tobe detected (N).

At step 950, a spectrum (e.g., including Raman scattering (or Ramansignal)) can be detected from the illuminated analyte. In someembodiments, the light (having the increased/decreased excitationwavelength) hitting the analyte results in Raman scattering (or Ramansignal) and fluorescence. For example, the Raman scattering can bedetected by spectrometer 210 and 210A (FIGS. 2 and 4) (e.g., usingdetector 280 through filter 270 (FIG. 2)). The detected Raman scatteringmay appear (e.g., when graphed/plotted) as shown in graph 600B (FIG. 6B)(where the excitation wavelength is the excitation wavelengthincreased/decreased by Δλ, for example, Δ₁. Each detected spectrum(e.g., data, graphical representation, and the like) can be stored by(and/or in) spectrometer 210 and 210A and/or computing system 295.

At step 960, a determination is made as to whether another spectrum isto be detected. In some embodiments, the predetermined number of spectrato be detected (N) is compared to the number of spectra (actually)detected. When the predetermined number of spectra to be detected (N) isless than the number of spectra detected, method 900 can proceed to step930. When the predetermined number of spectra to be detected (N) isequal to the number of spectra actually detected, method 900 can proceedto step 970. For example, when N=6 and spectra are already detected forλ₀, λ₁, λ₂, λ₃, λ₄, and λ₅, method 900 can proceed to step 970. By wayof further non-limiting example, when N=3 the detected Raman scatteringand fluorescence (e.g., detected for each of λ₀, λ₁, and λ₂) may appear(e.g., when graphed/plotted together) as shown in graphs 600A and/or600B (FIGS. 6A and 6B).

Optionally at step 970, a Raman spectrum of the analyte can be recoveredusing the detected spectra (e.g., N detected spectra). The recoveredRaman spectrum may appear (e.g., when graphed/plotted) as shown ingraphs 600A and 600B (FIGS. 6A and 6B) (e.g., Raman signal 630A and/or630B). Optionally at step 980, a molecule can be identified using therecovered Raman spectrum. For example, a database of known Ramanspectrum for certain molecules can be searched using (e.g., compared to)the recovered Raman spectrum to find a match.

Non-limiting examples of molecules that can be detected at step 980 areprovided in Table 2.

TABLE 2 MOLECULE DIAGNOSTIC FOR Carotenoid Antioxidant levels GlucoseDiabetes Daily Monitoring Glucose (HbA1c test) Diabetes Colon cancerbiomarker (BM) Cancer Liver cancer BM Cancer Lung cancer BM CancerMelanoma BM Cancer Stomach cancer BM Cancer HDL Cholesterol HeartDisease LDL Cholesterol Heart Disease Triglycerides Heart Disease

FIG. 10 illustrates an exemplary computer system 1000 that may be usedto implement some embodiments of the present invention. The computersystem 1000 in FIG. 10 may be implemented in the contexts of the likesof computing systems, networks, servers, or combinations thereof. Thecomputer system 1000 in FIG. 10 includes one or more processor unit(s)1010 and main memory 1020. Main memory 1020 stores, in part,instructions and data for execution by processor unit(s) 1010. Mainmemory 1020 stores the executable code when in operation, in thisexample. The computer system 1000 in FIG. 10 further includes a massdata storage 1030, portable storage device 1040, output devices 1050,user input devices 1060, a graphics display system 1070, and peripheraldevice(s) 1080.

The components shown in FIG. 10 are depicted as being connected via asingle bus 1090. The components may be connected through one or moredata transport means. Processor unit(s) 1010 and main memory 1020 areconnected via a local microprocessor bus, and the mass data storage1030, peripheral device(s) 1080, portable storage device 1040, andgraphics display system 1070 are connected via one or more input/output(I/O) buses.

Mass data storage 1030, which can be implemented with a magnetic diskdrive, solid state drive, or an optical disk drive, is a non-volatilestorage device for storing data and instructions for use by processorunit(s) 1010. Mass data storage 1030 stores the system software forimplementing embodiments of the present disclosure for purposes ofloading that software into main memory 1020.

Portable storage device 1040 operates in conjunction with a portablenon-volatile storage medium, such as a flash drive, floppy disk, compactdisk, digital video disc, or Universal Serial Bus (USB) storage device,to input and output data and code to and from the computer system 1000in FIG. 10. The system software for implementing embodiments of thepresent disclosure is stored on such a portable medium and input to thecomputer system 1000 via the portable storage device 1040.

User input devices 1060 can provide a portion of a user interface. Userinput devices 1060 may include one or more microphones, an alphanumerickeypad, such as a keyboard, for inputting alphanumeric and otherinformation, or a pointing device, such as a mouse, a trackball, stylus,or cursor direction keys. User input devices 1060 can also include atouchscreen. Additionally, the computer system 1000 as shown in FIG. 10includes output devices 1050. Suitable output devices 1050 includespeakers, printers, network interfaces, and monitors.

Graphics display system 1070 include a liquid crystal display (LCD) orother suitable display device. Graphics display system 1070 isconfigurable to receive textual and graphical information and processesthe information for output to the display device.

Peripheral device(s) 1080 may include any type of computer supportdevice to add additional functionality to the computer system.

The components provided in the computer system 1000 in FIG. 10 are thosetypically found in computer systems that may be suitable for use withembodiments of the present disclosure and are intended to represent abroad category of such computer components that are well known in theart. Thus, the computer system 1000 in FIG. 10 can be a personalcomputer (PC), hand held computer system, telephone, mobile computersystem, workstation, tablet, phablet, mobile phone, server,minicomputer, mainframe computer, wearable, or any other computersystem. The computer may also include different bus configurations,networked platforms, multi-processor platforms, and the like. Variousoperating systems may be used including UNIX, LINUX, WINDOWS, MAC OS,PALM OS, QNX, ANDROID, IOS, CHROME, and other suitable operatingsystems.

Some of the above-described functions may be composed of instructionsthat are stored on storage media (e.g., computer-readable medium). Theinstructions may be retrieved and executed by the processor. Someexamples of storage media are memory devices, tapes, disks, and thelike. The instructions are operational when executed by the processor todirect the processor to operate in accord with the technology. Thoseskilled in the art are familiar with instructions, processor(s), andstorage media.

In some embodiments, the computing system 1000 may be implemented as acloud-based computing environment, such as a virtual machine operatingwithin a computing cloud. In other embodiments, the computing system1000 may itself include a cloud-based computing environment, where thefunctionalities of the computing system 1000 are executed in adistributed fashion. Thus, the computing system 1000, when configured asa computing cloud, may include pluralities of computing devices invarious forms, as will be described in greater detail below.

In general, a cloud-based computing environment is a resource thattypically combines the computational power of a large grouping ofprocessors (such as within web servers) and/or that combines the storagecapacity of a large grouping of computer memories or storage devices.Systems that provide cloud-based resources may be utilized exclusivelyby their owners or such systems may be accessible to outside users whodeploy applications within the computing infrastructure to obtain thebenefit of large computational or storage resources.

The cloud is formed, for example, by a network of web servers thatcomprise a plurality of computing devices, such as the computing system1000, with each server (or at least a plurality thereof) providingprocessor and/or storage resources.

These servers manage workloads provided by multiple users (e.g., cloudresource customers or other users). Typically, each user places workloaddemands upon the cloud that vary in real-time, sometimes dramatically.The nature and extent of these variations typically depends on the typeof business associated with the user.

It is noteworthy that any hardware platform suitable for performing theprocessing described herein is suitable for use with the technology. Theterms “computer-readable storage medium” and “computer-readable storagemedia” as used herein refer to any medium or media that participate inproviding instructions to a CPU for execution. Such media can take manyforms, including, but not limited to, non-volatile media, volatile mediaand transmission media. Non-volatile media include, for example,optical, magnetic, and solid-state disks, such as a fixed disk. Volatilemedia include dynamic memory, such as system random-access memory (RAM).Transmission media include coaxial cables, copper wire and fiber optics,among others, including the wires that comprise one embodiment of a bus.Transmission media can also take the form of acoustic or light waves,such as those generated during radio frequency (RF) and infrared (IR)data communications. Common forms of computer-readable media include,for example, a floppy disk, a flexible disk, a hard disk, magnetic tape,any other magnetic medium, a CD-ROM disk, digital video disk (DVD), anyother optical medium, any other physical medium with patterns of marksor holes, a RAM, a programmable read-only memory (PROM), an erasableprogrammable read-only memory (EPROM), an electrically erasableprogrammable read-only memory (EEPROM), a Flash memory, any other memorychip or data exchange adapter, a carrier wave, or any other medium fromwhich a computer can read.

Various forms of computer-readable media may be involved in carrying oneor more sequences of one or more instructions to a CPU for execution. Abus carries the data to system RAM, from which a CPU retrieves andexecutes the instructions. The instructions received by system RAM canoptionally be stored on a fixed disk either before or after execution bya CPU.

Computer program code for carrying out operations for aspects of thepresent technology may be written in any combination of one or moreprogramming languages, including an object oriented programming languagesuch as Python, JAVA, SMALLTALK, C++ or the like and conventionalprocedural programming languages, such as the “C” programming languageor similar programming languages. The program code may execute entirelyon the user's computer, partly on the user's computer, as a stand-alonesoftware package, partly on the user's computer and partly on a remotecomputer or entirely on the remote computer or server. In the latterscenario, the remote computer may be connected to the user's computerthrough any type of wired and/or wireless network, including a(wireless) local area network (LAN/WLAN) or a (wireless) wide areanetwork (WAN/WWAN), or the connection may be made to an externalcomputer (for example, through the Internet using an Internet ServiceProvider, wireless Internet provider, and the like).

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present technology has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Exemplaryembodiments were chosen and described in order to best explain theprinciples of the present technology and its practical application, andto enable others of ordinary skill in the art to understand theinvention for various embodiments with various modifications as aresuited to the particular use contemplated.

Aspects of the present technology are described above with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer program instructions. These computer program instructions maybe provided to a processor of a general purpose computer, specialpurpose computer, or other programmable data processing apparatus toproduce a machine, such that the instructions, which execute via theprocessor of the computer or other programmable data processingapparatus, create means for implementing the functions/acts specified inthe flowchart and/or block diagram block or blocks.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or blockdiagram block or blocks.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods and computer program products according to variousembodiments of the present technology. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof code, which comprises one or more executable instructions forimplementing the specified logical function(s). It should also be notedthat, in some alternative implementations, the functions noted in theblock may occur out of the order noted in the figures. For example, twoblocks shown in succession may, in fact, be executed substantiallyconcurrently, or the blocks may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each block of the block diagrams and/or flowchart illustration, andcombinations of blocks in the block diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

The description of the present technology has been presented forpurposes of illustration and description, but is not intended to beexhaustive or limited to the invention in the form disclosed. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of the invention.Exemplary embodiments were chosen and described in order to best explainthe principles of the present technology and its practical application,and to enable others of ordinary skill in the art to understand theinvention for various embodiments with various modifications as aresuited to the particular use contemplated. The corresponding structures,materials, acts, and equivalents of all means or step plus functionelements in the claims below are intended to include any structure,material, or act for performing the function in combination with otherclaimed elements as specifically claimed. The description of the presenttechnology has been presented for purposes of illustration anddescription, but is not intended to be exhaustive or limited to theinvention in the form disclosed. Many modifications and variations willbe apparent to those of ordinary skill in the art without departing fromthe scope and spirit of the invention. Exemplary embodiments were chosenand described in order to best explain the principles of the presenttechnology and its practical application, and to enable others ofordinary skill in the art to understand the invention for variousembodiments with various modifications as are suited to the particularuse contemplated.

Aspects of the present technology are described above with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer program instructions. These computer program instructions maybe provided to a processor of a general purpose computer, specialpurpose computer, or other programmable data processing apparatus toproduce a machine, such that the instructions, which execute via theprocessor of the computer or other programmable data processingapparatus, create means for implementing the functions/acts specified inthe flowchart and/or block diagram block or blocks. These computerprogram instructions may also be stored in a computer readable mediumthat can direct a computer, other programmable data processingapparatus, or other devices to function in a particular manner, suchthat the instructions stored in the computer readable medium produce anarticle of manufacture including instructions which implement thefunction/act specified in the flowchart and/or block diagram block orblocks. The computer program instructions may also be loaded onto acomputer, other programmable data processing apparatus, or other devicesto cause a series of operational steps to be performed on the computer,other programmable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods and computer program products according to variousembodiments of the present technology. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof code, which comprises one or more executable instructions forimplementing the specified logical function(s). It should also be notedthat, in some alternative implementations, the functions noted in theblock may occur out of the order noted in the figures. For example, twoblocks shown in succession may, in fact, be executed substantiallyconcurrently, or the blocks may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each block of the block diagrams and/or flowchart illustration, andcombinations of blocks in the block diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

The description of the present technology has been presented forpurposes of illustration and description, but is not intended to beexhaustive or limited to the invention in the form disclosed. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of the invention.Exemplary embodiments were chosen and described in order to best explainthe principles of the present technology and its practical application,and to enable others of ordinary skill in the art to understand theinvention for various embodiments with various modifications as aresuited to the particular use contemplated.

What is claimed is:
 1. A method for spectroscopy comprising:illuminating, with a tunable laser, an analyte with a first light, thefirst light having a first excitation wavelength; detecting, with afiltered sensor, a first Raman signal, the filtered sensor being asingle photon avalanche diode array detector; illuminating, with thetunable laser, the analyte using a second light, the second light havinga second excitation wavelength, the second excitation wavelength beinglarger than the first excitation wavelength by a first predeterminedincrement; detecting, with the filtered sensor, a second Raman signal,the second Raman signal being shifted from the first Raman signal by asecond predetermined increment; illuminating, with the tunable laser,the analyte using a third light, the third light having a thirdexcitation wavelength, the third excitation wavelength being larger thanthe second excitation wavelength by the first predetermined increment;detecting, with the filtered sensor, a third Raman signal, the thirdRaman signal being shifted from the second Raman signal by the secondpredetermined increment, wherein the first Raman signal, the secondRaman signal, and the third Raman signal are directly passed by a beamsplitter from the analyte to the filtered sensor; constructing a Ramanspectrum, with a computing system, using the first Raman signal, thesecond Raman signal, and the third Raman signal; and determining atleast one molecule of the analyte, with the computing system, using theRaman spectrum and a database of predetermined Raman spectra.
 2. Themethod of claim 1, wherein the filtered sensor comprises a complementarymetal oxide semiconductor (CMOS) charge-coupled device (CCD) having afilter disposed thereon.
 3. The method of claim 2, wherein the CMOS CCDis back illuminated.
 4. The method of claim 2, wherein the filter is atleast one of a thin-film coating, glass, and plastic.
 5. The method ofclaim 2, wherein the first excitation wavelength, the second excitationwavelength, and the third excitation wavelength are each within a rangefrom 650 nm to 950 nm.
 6. The method of claim 1, wherein the filtercomprises a plurality of sub-filters, at least some of the plurality ofsub-filters transmitting light at different wavelength ranges, theplurality of sub-filters being arranged in at least one of aone-dimensional array and a two-dimensional array on the sensor.
 7. Themethod of claim 1, wherein the tunable laser is at least one oftemperature controlled and in a transistor outline (TO) package.
 8. Themethod of claim 1, wherein the analyte is at least one of living planttissue, animal tissue, and a human limb.
 9. The method of claim 1,wherein the illuminating the analyte using the first light, thedetecting the first Raman signal, the illuminating the analyte using thesecond light, the detecting the second Raman signal, the illuminatingthe analyte using third light, and the detecting the third Raman signalare collectively performed in 25 seconds or less.
 10. The method ofclaim 1, wherein the at least one molecule is one or more of bloodsugar, cholesterol, and a cancer biomarker.
 11. A system forspectroscopy comprising: a processor; and a memory communicativelycoupled to the processor, the memory storing instructions executable bythe processor to perform a method, the method comprising: illuminating,with a tunable laser, an analyte with a first light, the first lighthaving a first excitation wavelength; detecting, with a filtered sensor,a first Raman signal, the filtered sensor being a single photonavalanche diode array detector; illuminating, with the tunable laser,the analyte using a second light, the second light having a secondexcitation wavelength, the second excitation wavelength being largerthan the first excitation wavelength by a first predetermined increment;detecting, with the filtered sensor, a second Raman signal, the secondRaman signal being shifted from the first Raman signal by a secondpredetermined increment; illuminating, with the tunable laser, theanalyte using a third light, the third light having a third excitationwavelength, the third excitation wavelength being larger than the secondexcitation wavelength by the first predetermined increment; detecting,with the filtered sensor, a third Raman signal, the third Raman signalbeing shifted from the second Raman signal by the second predeterminedincrement, wherein the first Raman signal, the second Raman signal, andthe third Raman signal are directly passed by a beam splitter from theanalyte to the filtered sensor; constructing a Raman spectrum using thefirst Raman signal, the second Raman signal, and the third Raman signal;and determining at least one molecule of the analyte using the Ramanspectrum and a database of predetermined Raman spectra.
 12. The systemof claim 11, wherein the filtered sensor comprises a complementary metaloxide semiconductor (CMOS) charge-coupled device (CCD) having a filterdisposed thereon.
 13. The system of claim 12, wherein the CMOS CCD isback illuminated.
 14. The system of claim 12, wherein the filter is atleast one of a thin-film coating, glass, and plastic.
 15. The system ofclaim 12, wherein the first excitation wavelength, the second excitationwavelength, and the third excitation wavelength are each within a rangefrom 650 nm to 950 nm.
 16. The system of claim 11, wherein the filtercomprises a plurality of sub-filters, at least some of the plurality ofsub-filters transmitting light at different wavelength ranges, theplurality of sub-filters being arranged in at least one of aone-dimensional array and a two-dimensional array on the sensor.
 17. Thesystem of claim 11, wherein the tunable laser is at least one oftemperature controlled and in a transistor outline (TO) package.
 18. Thesystem of claim 11, wherein: the analyte is at least one of living planttissue, animal tissue, and a human limb; and the at least one moleculeis one or more of blood sugar, cholesterol, and a cancer biomarker. 19.The system of claim 11, wherein the illuminating the analyte using thefirst light, the detecting the first Raman signal, the illuminating theanalyte using the second light, the detecting the second Raman signal,the illuminating the analyte using third light, and the detecting thethird Raman signal are collectively performed in 25 seconds or less. 20.A system for spectroscopy comprising: means for illuminating an analytewith a first light, the first light having a first excitationwavelength; means for detecting a first Raman signal, a filtered sensorbeing a single photon avalanche diode array detector; means forilluminating the analyte using a second light, the second light having asecond excitation wavelength, the second excitation wavelength beinglarger than the first excitation wavelength by a first predeterminedincrement; means for detecting a second Raman signal, the second Ramansignal being shifted from the first Raman signal by a secondpredetermined increment; means for illuminating the analyte using athird light, the third light having a third excitation wavelength, thethird excitation wavelength being larger than the second excitationwavelength by the first predetermined increment; means for detecting athird Raman signal, the third Raman signal being shifted from the secondRaman signal by the second predetermined increment, wherein the firstRaman signal, the second Raman signal, and the third Raman signal aredirectly passed by a beam splitter from the analyte to the filteredsensor; means for constructing a Raman spectrum using the first Ramansignal, the second Raman signal, and the third Raman signal; and meansfor determining at least one molecule of the analyte using the Ramanspectrum and a database of predetermined Raman spectra.